Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency

Collagen VI is an extracellular matrix protein that forms a microfilamentous network in skeletal muscles and other organs. Inherited mutations in genes encoding collagen VI in humans cause two muscle diseases, Bethlem myopathy and Ullrich congenital muscular dystrophy. We previously generated collagen VI-deficient (Col6a1-/-) mice and showed that they have a muscle phenotype that strongly resembles Bethlem myopathy. The pathophysiological defects and mechanisms leading to the myopathic disorder were not known. Here we show that Col6a1-/- muscles have a loss of contractile strength associated with ultrastructural alterations of sarcoplasmic reticulum (SR) and mitochondria and spontaneous apoptosis. We found a latent mitochondrial dysfunction in myofibers of Col6a1-/- mice on incubation with the selective F1F(O)-ATPase inhibitor oligomycin, which caused mitochondrial depolarization, Ca2+ deregulation and increased apoptosis. These defects were reversible, as they could be normalized by plating Col6a1-/- myofibers on collagen VI or by addition of cyclosporin A (CsA), the inhibitor of mitochondrial permeability transition pore (PTP). Treatment of Col6a1-/- mice with CsA rescued the muscle ultrastructural defects and markedly decreased the number of apoptotic nuclei in vivo. These findings indicate that collagen VI myopathies have an unexpected mitochondrial pathogenesis that could be exploited for therapeutic intervention.     

Antiviral strategies against influenza virus: towards new therapeutic approaches

Influenza viruses are major human pathogens responsible for respiratory diseases affecting millions of people worldwide and characterized by high morbidity and significant mortality. Influenza infections can be controlled by vaccination and antiviral drugs. However, vaccines need annual updating and give limited protection. Only two classes of drugs are currently approved for the treatment of influenza: M2 ion channel blockers and neuraminidase inhibitors. However, they are often associated with limited efficacy and adverse side effects. In addition, the currently available drugs suffer from rapid and extensive emergence of drug resistance. All this highlights the urgent need for developing new antiviral strategies with novel mechanisms of action and with reduced drug resistance potential. Several new classes of antiviral agents targeting viral replication mechanisms or cellular proteins/processes are under development. This review gives an overview of novel strategies targeting the virus and/or the host cell for counteracting influenza virus infection.     

加工条件对聚丙烯釜内合金结构及性能影响

运用动态力学分析(DMA)、差示扫描量热法(DSC)、流变分析等手段研究了加工条件对聚丙烯釜内合金结构的影响,并结合力学性能表征建立了结构与性能的关系.研究结果表明,在设定的加工条件下,聚丙烯釜内合金的熔融结晶特性和流变性能基本上没有变化.聚丙烯和乙丙橡胶组份间的相容性却随密炼加工温度的增加得到了明显的改善,来源于剪切诱导组份间的相互扩散.高温密炼加工的聚丙烯釜内合金拉伸断裂伸长率表现出了显著的提高.     

可拓学理论在住宅建筑综合性能评价中的应用

将可拓理论与住宅建筑综合性能评价相结合,以物元理论和可拓数学作为其理论框架,把住宅建筑综合性能评价看成一个复杂的、相互联系的物元网,并在物元理论、可拓集合论和关联函数运算的基础上,以一套实际住宅为例,建立了住宅建筑综合性能评价的物元模型,利用此模型对住宅建筑综合性能作出了客观评价,结果表明该方法是可行的,且效果理想,是一种既可行又容易被人们接受的评价方法。     

含联苯结构环氧树脂/蒙脱土纳米复合材料的制备及其固化反应动力学

采用含联苯结构环氧树脂3,3＇,5,5＇-四甲基联苯二酚二缩水甘油醚(TMBP)与层间距为2.33 nm的有机蒙脱土(O-MMT)进行插层复合,并选用芳香型固化剂4,4 ＇-二氨基二苯甲烷(DDM),制备了TMBP/DDM/MMT纳米复合材料.采用非等温差示扫描量热法(DSC)研究该体系的固化反应动力学,求得其表观活化...     

一种自相似业务量预测的卡尔曼滤波算法

针对网络拥塞控制中不能准确预测自相似业务量的问题,提出了一种噪声在线估计卡尔曼滤波(NOEKF)算法.NOEKF算法不依赖于业务源反馈信息,通过观测节点处当前和过去时刻的业务量来预测下一时刻的业务量,并建立了业务量的卡尔曼滤波状态方程和观测方程,给出了递推形式的状态向量最佳估计形式.考虑到未知状态方程和观测方程噪声的统计特性,采用在线估值法,并引入遗忘因子对噪声的统计特性进行估计.NOEKF算法预测准确、偏差小.仿真结果表明,与经典卡尔曼滤波算法和时间序列预测方法比较,NOEKF算法能够更精确地预测自相似业务量,预测误差可降低60%以上.     

地铁火灾的盐水实验与计算机数值模拟

为了认识地铁火灾烟气的流动规律，达到为消防设计提供相关资料并采取合理消防措施的目的，采用缩尺盐水实验与计算机计算流体力学数值模拟相结合的方法对地铁火灾进行研究．研究受限空间火灾烟气运动的手段主要有全尺寸火灾实验、小尺寸模拟实验和计算机数值模拟3种．实验模拟了列车着火和站台着火2种情况，得到了地铁火灾的烟气流动规律，比较并分析了计算流体力学数值模拟与盐水实验得出的烟层无量纲高度和无量纲时间．计算流体力学数值模拟与盐水实验得到的烟气到达楼梯口所需时间相差为1．5—2s，到达远侧楼梯口所需时间相差7．2s．二者之间存在着一定的误差，但误差不大．同一时刻，数值模拟比盐水实验得到的无量纲烟层高度高0．1左右，变化趋势一致．结果表明，实验条件选取合理，方程模型选用和边界条件设置恰当，盐水实验与计算流体力学数值方法模拟地铁火灾均是可行的．     

The p66shc adaptor protein controls oxidative stress response and life span in mammals

Gene mutations in invertebrates have been identified that extend life span and enhance resistance to environmental stresses such as ultraviolet light or reactive oxygen species. In mammals, the mechanisms that regulate stress response are poorly understood and no genes are known to increase individual life span. Here we report that targeted mutation of the mouse p66shc gene induces stress resistance and prolongs life span. p66shc is a splice variant of p52shc/p46shc (ref. 2), a cytoplasmic signal transducer involved in the transmission of mitogenic signals from activated receptors to Ras. We show that: (1) p66shc is serine phosphorylated upon treatment with hydrogen peroxide (H2O2) or irradiation with ultraviolet light; (2) ablation of p66shc enhances cellular resistance to apoptosis induced by H2O2 or ultraviolet light; (3) a serine-phosphorylation defective mutant of p66shc cannot restore the normal stress response in p66shc-/- cells; (4) the p53 and p21 stress response is impaired in p66shc-/- cells; (5) p66shc-/- mice have increased resistance to paraquat and a 30% increase in life span. We propose that p66shc is part of a signal transduction pathway that regulates stress apoptotic responses and life span in mammals.     

温敏性大孔聚(丙烯酰胺-co-N-异丙基丙烯酰胺)微球在固定化果胶酶中的应用

采用在反相悬浮聚合中加入致孔剂的方法制备温敏性大孔PAM-co-PNIPAM微球,并以该微球为载体固定化果胶酶,探讨了温度、pH值、时间、加酶量、戊二醛浓度、交联温度、交联时间对果胶酶固定化效果的影响,同时对固定化果胶酶的酶学特性进行研究.结果表明:该微球具有很好的比表面积和温度敏感性;当固定化果胶酶的载酶量高达322.6mg/g时,载体本身仍能保持较好的稳定性.固定化果胶酶在pH为3.0～4.5,温度为50～60℃的范围内仍能保持较高的酶催化活性.在存储30d后固定化酶的活性仍能保持为原来的80%左右,而且具有较高的操作稳定性,在连续使用20次后,仍有68%以上的活性.     

基于CO2地质储存工程的CO2增强地热系统中CO2注入温度对热储层热提取率影响分析——基于鄂尔多斯CCS工程

 以鄂尔多斯CO₂地质储存工程区马家沟组地层为人工地热储层,用TOUGH2软件建立以CO₂为传热载体的CO₂-EGS模拟模型,设计并模拟了5种不同的CO₂注入温度(18～42℃)条件下CO₂-EGS系统运行特征,分析了CO₂注入温度对热提取率和系统可持续性的影响。结果表明,5种方案的热量提取率在CO₂-水驱替阶段变化区间为6.37～7.9MW,在液相流消失阶段变化区间为6.64～8.68MW。整个CO₂-EGS系统运行期的平均地层热提取率为6.56～8.47MW,系统可持续时间10.58～11.49a,系统运行期温度下降速率为1.89～1.74℃/a。CO₂的注入温度对深层地热能系统热量提取率影响显著,对系统的可持续性影响较小。为了获得最大的经济效益,应在CO₂-EGS运行允许范围内减小CO₂的注入温度。研究成果可以为CO₂地质储存与资源化利用提供参考。